The proposed investigation would study the mechanisms of action of ethanol, and the neural adaptation process upon its chronic exposure and withdrawal. The aim is to understand the mechanisms of these processes so that strategies can be developed for new treatment regimens, and the pathophysiology associated with alcohol abuse and alcoholism might be diminished. Alcohol abuse and alcoholism in humans has devastating consequences to the mental, physical, and social health of those afflicted. At the present time, there is no pharmacotherapy for alcoholism or the pathologic effects of alcohol on the central nervous system (CNS). The understanding of the mechanisms of action of ethanol, and the neural adaptation during and after chronic ethanol exposure may help to develop new leads for the treatment of alcohol abuse and alcoholism. For example, at the present, benzodiazepines are used empirically in the treatment of alcohol withdrawal. However, the benzodiazepines are also addictive and can produce an abstinence syndrome upon withdrawal. It is therefore desirable to find alternative therapies. Studying the action of alcohol on the excitatory amino acid receptor systems may aid in the development of such therapies. The action of ethanol, and neural adaptation during and after a course of chronic ethanol exposure will be examined in cultured CNS neurons. The pharmacodynamic (functional) effect of ethanol will be monitored using electrophysiologic methods.